Support is requested for a Keystone Symposia meeting entitled Autoimmunity and Tolerance, organized by Jane L. Grogan, Joanne L. Viney and Gerald T. Nepom. The meeting will be held in Keystone, Colorado from February 3-8, 2015. Understanding immune regulation in autoimmunity and tolerance is important for delivering therapies to patients with uncontrolled autoimmune disease. Therefore, the goal of this Keystone Symposia meeting is to bring together scientists and clinicians to discuss what we are learning from preclinical mouse models and patient studies. In this regard, the past decade has seen the translation of our fundamental understanding of the immune response into clinical studies, with some success and also some failures. These clinical outcomes, coupled with more sophisticated techniques available to interrogate the human immune response, allow us to reassess and further explore pathways that are driving autoimmune disease. In this symposium, we cover the pathways in immunity and tolerance that lead to loss of immunological control, dysregulated immune responses and chronic inflammatory disease. We cover preclinical and clinical aspects of a diverse number of autoimmune and inflammatory diseases including lupus, multiple sclerosis, inflammatory bowel disease, psoriasis, transplantation and rheumatoid arthritis. Each session is designed to include a basic research talk followed by a mechanistic talk on mouse and human and clinical translation. The general topic of this meeting is relevant to the NIAID mission with respect to the broad area of autoimmunity.